Increased renal biosynthesis of prostaglandin E2 and thromboxane B2 in human congenital obstructive uropathy.
Animal experiments have shown that after ureter obstruction hydronephrotic kidneys release increased amounts of prostaglandin E2 (PGE2) and thromboxane A2 (TxA2), suggesting that these prostanoids modify renal blood flow and excretory function in this model. To test the hypothesis that these mechanisms are also operative in congenital obstructive uropathy, we measured prostanoid excretion rates in 12 neonates and infants with congenital unilateral or bilateral hydronephrosis. Prostanoid determinations were performed by gas chromatography mass spectrometry. PGE2 and thromboxane B2 (TxB2) (non-enzymatic metabolite of TxA2) excretion exceeded the normal range in eight and 11 of 12 patients, respectively. Median PGE2 excretion was 22, range 4-572 ng/h/1.73 m2 (normal 3-16). Median TxB2 excretion was 22, range 3-188 ng/h/1.73 m2 (normal 3-7). No other renal prostanoids (prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha) or systemic prostanoid metabolites (PGE-M, 2,3-dinorthromboxane B2, 11-dehydro-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1 alpha) were consistently elevated. A second group of 12 neonates with congenital obstructive uropathy was followed sequentially. PGE2 and thromboxane B2 excretion rates increased even further after surgical decompression and gradually normalized during follow-up. There was a significant relationship between elevated FeNa and enhanced PGE2 and TxB2 excretion. These data suggest that endogenous renal formation of PGE2 and TxA2 is selectively stimulated in hydronephrotic kidneys in neonates and infants. PGE2 and TxA2 may be involved in modulating renal function in these infants.
Kühl
P G
PG
Department of Pediatrics, University of Heidelberg, Federal Republic of Germany.
Schönig
G
G
Schweer
H
H
Seyberth
H W
HW
D002675:Child, Preschool; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006869:Hydronephrosis / Q000151:congenital* / Q000209:etiology / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism*; D008297:Male; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000150:complications / Q000151:congenital* / Q000378:metabolism
D013929:Thromboxane B2; D015232:Dinoprostone